989 research outputs found

    Freedom of Information

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    OBJECTIVE: It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. DESIGN: Randomized controlled trial. SETTING: University animal laboratory. SUBJECTS: Domestic piglets (n = 30). INTERVENTIONS: Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. MEASUREMENTS AND MAIN RESULTS: Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. CONCLUSIONS: This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion

    Clinical translation of a regeneration strategy for spinal cord injury

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    The complex and vulnerable tissue of the spinal cord does not heal after injury, leaving patients with lifelong disability after spinal cord injury (SCI). Many milestones have been reached during the last century through specialized centers for SCI, greatly increasing life expectancy and quality of life by battling common medical problems such as urinary tract infections, pressure ulcers, spasticity, neurogenic pain, and sexual function as well as providing means of rehabilitation to a meaningful and productive life after SCI. Despite the advances in preclinical knowledge of mechanisms in SCI and several clinical trials completed, to date no pivotal treatment exists for acute spinal cord injury or for the regeneration of lost function in the chronic state. The first reports of experimental regeneration of central axons through peripheral nerve grafts are more than a century old. In the last decades, regeneration of function after SCI has been reported by several research groups in different species using peripheral nerve grafts and FGF1. The regeneration strategy was furthered refined in our group by the use of a biodegradable scaffold for exact positioning of the nerve grafts. This thesis describes the translational process to reach a clinical trial of glial scar resection and implantation of peripheral nerve grafts and FGF1 using a biodegradable guiding scaffold. In paper I, we show that both the cranial and caudal demarcation of a thoracic spinal cord injury can be defined with electromyography of intercostal muscles in chronic SCI patients. We also present an MRI protocol with acceptable image contrast despite the presence of spinal instrumentation and showed that the injury length found with electromyography correlates well with length of injury on MRI. In paper II, we use a novel conversion table between spinal cord neuronal segments and vertebral segments and combine data on human spinal cord cross-sectional diameters from different published sources to yield continuous estimates on human spinal cord size and variability. In paper III, we describe the design of a set of spinal cord injury guiding devices based on the data from paper II, covering the normal variability found in human thoracic spinal cord segments T2–T12 with an acceptable error-of-fit for the elliptical shape as well as guiding channels proposed. In paper IV, we detail the adverse events reported during the first 60 days postoperatively in the ongoing clinical trial “Safety and Efficacy of SC0806 (Fibroblast Growth Factor 1 and a Device) in Traumatic Spinal Cord Injury Subjects.” Early results from the first six complete (AIS-A) thoracic spinal cord injury subjects operated on in the ongoing trial show that with precise preoperative and intraoperative neurophysiology, surgery and implantation can be performed without negative effects on neurological level, and safety and tolerability are acceptable to merit the continuation of the trial. In paper V, we describe the construction of a cost-effective light-sheet microscope by modification of an outdated microarray-scanner. The microscope was applied to an experimental model of hypoglossal nerve avulsion injury, and proliferation of Iba1+ cells could be quantified automatically demonstrating a possible application of the microscope. In conclusion, reaching clinical trial in a translational process is a significant and collaborative undertaking requiring co-operation of multiple institutions and professions as well as rigorous external control of data quality and adverse events to ensure safety of study subjects. The papers in this thesis detail some relevant steps necessary for the clinical translation of regeneration strategies in chronic SCI

    The Challenge of Cooperative Regulatory Relations After Enlargement

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    This paper conceptualises European governance as a continuous series of collective action games among national regulators. European administration is theorized as a set of mutually beneficial relations among independent regulators, rather than as a hierarchy of supranational institutions, courts, and national administrators. The collective action approach highlights the importance of certain factors in fostering regulatory cooperation and enabling the common market to become an administrative reality: repeated interactions, monitoring and sanctioning by the Commission and the courts, reciprocity norms, and trust. It also suggests that one of the most significant challenges of enlargement will be to establish cooperative regulatory exchanges among old and new regulators. Regulators in the existing member states do not always trust the capacity of Central and Eastern European regulators to administer the acquis communautaire. Cooperation and trust among old and new regulators will also prove difficult because, after enlargement, their relations will gradually shift from ones of power to ones of mutually beneficial exchanges among equals. The solution lies in self-awareness of the structure of the collective action game, a more active role for the Commission and the Court in monitoring compliance, and strict adherence to a strategy of reciprocity in retaliating for non-compliance

    Measuring the environmental footprint of leather processing technologies

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    The selection of materials and manufacturing processes often determines most of the environmental impact that a product will have during its life cycle. In directing consumption toward products with the least impact on the environment, measuring and comparing material alternatives with site‐specific data is a fundamental prerequisite. Within the apparel and footwear industry, some famous brands have recently been basing their advertising on the claim that vegetable‐tanned leather is more environmentally friendly than chromium‐tanned leather. However, there is a lack of scientific research assessing and comparing vegetable‐ and chromium‐tanned leather in a wider context than the toxicity of chromium. To fill this gap, this study measured and compared the carbon, water, and energy footprint of vegetable and chromium leather processing technology and intermediate processing stages in 12 selected tanneries in seven different countries worldwide. Each tannery proved to be very individual, and therefore attempting to perform this type of analysis without simply producing meaningless generalities is a challenge for companies, researchers, and regulators. The variability in results demonstrates that secondary data for the tanning phase should be utilized with caution in a decision‐making context. The use of primary data would be advisable for life cycle assessment studies of leather goods. No significant differences were found in the footprint of vegetable and chromium leather processes, but these are only indicative findings and need confirmation in further studies. An important area needing investigation is then how a fair comparison can be made between renewable natural materials and nonrenewable materials used in both leather‐processing technologies

    Alga-made anti-Hepatitis B antibody binds to human Fcγ receptors.

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    Microalgae are unicellular eukaryotic organisms which represent an emerging alternative to other cell biofactories commonly used to produce monoclonal antibodies. Microalgae display several biotechnological advantages such as their rapid growth rate and their phototrophic lifestyle allowing low production costs as protein expression is solar-fueled. Recently, a fully assembled recombinant IgG antibody directed against Hepatitis B surface antigen is produced and secreted in the culture medium of the diatom Phaeodactylum tricornutum. A biochemical characterization of this recombinant antibody demonstrated that the Asn-297 is N-glycosylated by oligomannosides. In the immune system, antibodies interact with effector molecules and cells through their Fc part and the recognition of Fcγ receptors (FcγR) which are important for inducing phagocytosis of opsonized microbes. Interactions between IgG and FcγR are influenced by the N-glycan structures present on the Asn-297. In this study, the authors characterized the binding capacity of the anti-hepatitis B recombinant IgG produced in P. tricornutum to two human Fcγ receptors (FcγRI and IIIa) using a cellular binding assay and surface plasmon resonance (SPR). This allowed us to demonstrate that the alga-made antibody is able to bind FcγRI with a reduced affinity and engages FcyRIIIa with 3-times higher affinity compared to a control human IgG1

    Material Sustainability and Patient’s Experiences of Silver Tracheostomy Tubes-An In-Vitro and In-Vivo Case Study

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    Introduction: Tracheostomy tubes are used for enabling a free airway for patients with respiratory failures. In trachea, tracheostomy tubes are exposed to the alkaline tracheal secretion and lining fluid containing proteins, enzymes, organic acids, inorganic salts, and bacteria. Research shows severe material degradation of tracheostomy tubes made of polymeric materials after patient use. Silver tracheostomy tubes are made for long-term exposure up to several years. The objectives were a) To evaluate and describe the performance and durability of sterling silver tracheostomy tubes, b) To preliminarily describe and discuss the resulting morphological changes of the material surface after 6 months of clinical use c) To describe the patient’s own experiences of having a silver tracheostomy tube for a prolonged period of time and d) To study the release rate of metal ions into synthetic biological fluids in-vitro. Methods: Two different brands of silver tracheostomy tubes were studied in-vitro in synthetic body fluids. Six patients with silver tracheostomy tubes were included for long-term study of 6 months. Scanning Electron Microscopy was used to evaluate surface changes on the tube material. Patient’ s experiences were measured with a study specific questionnaire with open ended questions. Results: There were initial irregularities and defects on the reference silver tubes. A significant difference in material degradation between the tube brands were found after patient use. The release rate of metal ions into synthetic biological fluids revealed higher concentrations of copper ions than of silver ions. Patient´s own experiences revealed the importance of having a properly fitted tube to avoid complications. Conclusion: There was severe degradation on all tubes and significant differences between the tube brands. Patients found it important with a properly fitted tube which could make it possible for them to live a good life despite the chronic tracheostomy. Keywords: Respiratory Care; Tracheostomy Tube; Silver; Material Degradation; Patient Experience; Chronic Tracheostomy Abbreviations: PVC: polyvinylchloride; PU: polyurethane; NRC: National Respiratory Centre; SEM: Scanning electron microscopy; EDX: Energy- Dispersive X-Ray Spectroscopy; SBF: Simulated Biological Fluids; ALF: Artificial Lysosomal Fluid; ALF: Artificial Lysosomal Fluid; FAAS: Flame Atomic Absorption Spectroscopy; OSHA: Occupational Safety and Health AdministrationpublishedVersio
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